Convection-enhanced delivery of ¹³¹I-chTNT-1/B mAB for treatment of high-grade adult gliomas

Abstract

Introduction: Despite treatment advances for malignant gliomas in adults, prognosis remains poor, largely due to the infiltrative and heterogeneous biology of these tumors. Response to adjuvant therapy is not always uniform and the blood–brain barrier prevents the majority of chemotherapeutics from adequately reaching primary tumor sites. These obstacles necessitate development of novel delivery methods and agents.

Areas covered: ¹³¹I-chTNT-1/B mAB (Cotara) is a genetically engineered chimeric monoclonal antibody that binds to the DNA–histone H1 complex. It carries ¹³¹I, which delivers sufficient energy to kill adjacent tumor cells. Through convection-enhanced delivery (CED) it provides radioimmunotherapy directly to the resection cavity. We review the pharmacology and clinical experience with ¹³¹I-chTNT-1/B mAB, detailing results of completed Phase I and II trials.

Expert opinion: Novel agents and therapeutic modalities, such as ¹³¹I-chTNT-1/B mAB, are of interest for treatment of malignant glioma, for which the prognosis continues to be dismal. ¹³¹I-chTNT-1/B mAB targets tumor cells and radioisotope labeling allows radiation delivery to the tumor with sharp fall-off. Data from Phase I and II trials of CED delivery of ¹³¹I-chTNT-1/B mAB shows it is well tolerated. Phase II trial data suggests it could be promising therapeutically, though conclusions about efficacy require further trials and clinical experience. The compound is currently in a Phase II trial for dose confirmation in patients with malignant gliomas.

Keywords::

• ¹³¹I-chTNT-1/B mAB
• convection-enhanced delivery
• Cotara
• glioblastoma multiforme
• high grade gliomas
• malignant glioma
• radioimmunotherapy
• tumor necrosis therapy